# Channelopathy-Associated Epilepsy Research Center

> **NIH NIH U54** · NORTHWESTERN UNIVERSITY · 2020 · $47,992

## Abstract

PROJECT SUMMARY
Channelopathies, particularly those involving voltage-gated sodium (NaV) and potassium (KV) channel genes,
are responsible for a variety of epilepsy syndromes having diverse clinical severity. Further, NaV and KV
channels are important targets for many approved and investigational anticonvulsant drugs. Among the many
genes associated with epilepsy, those encoding NaV and KV channels have the highest cumulative variant
burden (>2,000 variants in the Human Gene Mutation Database), accounting for approximately one third of all
reported genetic variants associated with epilepsy and related neurodevelopmental disorders. But
differentiating pathogenic from benign variants and establishing genotype-phenotype relationships has become
increasingly challenging because of explosive growth in the number of variants discovered in research and
clinical medicine. Channelopathy-associated epilepsies represent unique opportunities to meet the challenge
of variant annotation because well-established in vitro functional assay paradigms exist for these proteins,
coupled with extensive knowledge regarding their contributions to neuronal function and drug response.
We propose to create a multi-institutional and interdisciplinary CHANNELOPATHY-ASSOCIATED EPILEPSY
RESEARCH CENTER that will combine high-throughput technologies with high-content human neuron and
animal model systems. The Center will consist of three integrated research projects and two scientific cores
involving a synergistic mixture of academic and industry scientists. Project 1 will conduct a large-scale
functional evaluation of variants in genes encoding voltage-gated ion channels frequently associated with
monogenic epilepsy, then curate findings in tandem with revised variant classifications. Project 2 will
investigate human neuron models of channelopathy-associated epilepsy using conventional
electrophysiological methods and an especially innovative, industrial optogenetic approach (Optopatch) to
stimulate and record data from hundreds of neurons simultaneously with single-cell precision. Project 3 will
develop and investigate new mouse models of channelopathy-associated epilepsy and compare variant ion
channel dysfunction across model systems. Projects will be aided by collaboration with a Variant Prioritization
and Curation Core and a Mutagenesis and Cell Expression Core. A key objective of our Center is to determine
to what extent non-neuronal cell models can predict effects of ion channel variants in neurons and brain. Our
overarching goal is to promote transformative advances in our understanding of the functional consequences
of genetic variants in channelopathy-associated epilepsy, and to enable a paradigm shift to a gene/variant-
based taxonomy of epilepsy that harmonizes with traditional clinical classification schemes while guiding the
implementation of precision medicine.

## Key facts

- **NIH application ID:** 10054599
- **Project number:** 3U54NS108874-02S1
- **Recipient organization:** NORTHWESTERN UNIVERSITY
- **Principal Investigator:** Alfred L. George
- **Activity code:** U54 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $47,992
- **Award type:** 3
- **Project period:** 2018-09-30 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10054599

## Citation

> US National Institutes of Health, RePORTER application 10054599, Channelopathy-Associated Epilepsy Research Center (3U54NS108874-02S1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10054599. Licensed CC0.

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